Project Summary/Abstract Obesity exacerbates age-related declines in function, is a strong determinant of mobility disability, and is associated with poorer clinical outcomes and quality of life. Given that over one-third of older adults are obese and the public health burden of age-related disability, identifying effective therapies that prevent obesity-related declines in function and health in older adults are urgently needed. Clinical trials by our group and others show that diet-induced weight loss interventions, particularly when combined with exercise, improve body composition and physical and metabolic function over the short-term (in the weight-reduced state) in obese older adults. However, the overall safety and long-term benefits of intentional weight loss in this population remain controversial and weight loss is often not recommended because of uncertainty of whether the benefits outweigh the risks (e.g., loss of muscle mass and bone). Furthermore, most individuals are not successful at long-term maintenance of weight loss. Thus, whether improvements in physical and metabolic function and other health parameters persist over time among older adults following intentional weight loss, particularly if weight regain occurs, is unknown. The overall goals of the proposed study are to determine if the short-term benefits of intentional weight loss on physical and metabolic function are sustained and to examine potential long-term benefits and risks of weight loss in older adults. We will determine the effects of randomization to diet-induced weight loss on physical function (primary outcome), body composition, bone mineral density, and cardiovascular risk factors (secondary aims) a minimum of 3 and a maximum of 10 years after intervention completion. Our general hypothesis is that randomization to weight loss will result in improved long-term physical and metabolic function compared to randomization to no weight loss. We will take advantage of our unique access to five NIH-supported randomized, controlled trials that enrolled overweight or obese (BMI?27 kg/m2) older adults (mean age at randomization, 67.3 years) and randomized them to weight loss plus exercise (n=458) or exercise alone (n=396) at Wake Forest from 2005 to 2014, the pooling of which will provide sufficient sample size to definitively evaluate the long-term functional and health consequences of prior intentional weight loss. We will also explore the long-term effects of randomization to weight loss on quality of life (SF-36), obesity- and weight loss-related medical events (e.g., knee replacements, fractures, MI), hospitalizations, and mortality; and assess the role of current behaviors (e.g., dietary intake, physical activity) on weight loss maintenance, physical function, body composition, and cardiovascular risk factors. The proposed study will be the first randomized, controlled design to examine the long-term effects of intentional weight loss in older adults and builds on our Aging Center's collaborative research focus in geriatric obesity treatment to answer compelling and clinically important questions regarding the long-term efficacy and safety of weight loss interventions in older adults in an efficient and cost-effective manner.